Various techniques for formulating active ingredients are known in order to selectively control the resultant release rate of the drug, e.g., via sustained release, slow release, fast release, etc. Often, it is not only important to control the release rate, but also to control the shape of the release curve, i.e., the functional dependence of the in vivo concentration of the drug versus time. Simultaneous attainment of both goals is generally most difficult.
Firstly, it is important for any pharmaceutical formulation technique to provide the capability of preselecting a desired release rate which can be tailored to the unique characteristics of each drug. For example, many formulations exist which permit selection of very slow release rates, i.e., sustained release formulations. (See, e.g., U.S. Pat. No. 3,641,236 based upon glycerol fatty acid esters and U.S. Pat. No. 3,950,508 based upon alkyl celluloses and inert powders such as talc, which, in combination with other ingredients, produce a gradual disaggregation of the sustained release tablet.) These can often cause toxicity and other side effects due to an inordinately long presence of the drug in the body. Thus, methods of preselecting somewhat faster release rates, i.e., slow release rates--midway between fast and sustained rates--are needed.
Moreover, many formulations result in a release curve having a high concentration peak at the beginning of release which subsequently tails off at longer times (see, e.g., curve (----) of FIG. 1). Such concentration peaks are generally undesirable since they can lead to toxicity and/or other adverse side effects. Additionally, their existence significantly limits the freedom to increase the unit dosage of administration. Such an increased dosage would correspondingly increase the peak concentration. Under such circumstances, it is not possible to decrease the frequency of administration by increasing the unit dosage. This is a significant disadvantage since it is well established that the likelihood that a patient will fail to take doses of his medication is directly proportional to the required frequency of administration.
As can be seen, in very many instances, it is most desirable to achieve both a relatively slow release rate of medication and a minimal peak concentration. These should further be selectable so that the resultant in vivo absorption is desirably controlled and the bioavailability of the drug is maximized.